CN103142990B - Medicine for treating animal bacterial diseases and preparation method thereof - Google Patents
Medicine for treating animal bacterial diseases and preparation method thereof Download PDFInfo
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- CN103142990B CN103142990B CN201310082473.6A CN201310082473A CN103142990B CN 103142990 B CN103142990 B CN 103142990B CN 201310082473 A CN201310082473 A CN 201310082473A CN 103142990 B CN103142990 B CN 103142990B
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Abstract
The invention relates to a medicine for treating animal bacterial diseases and a preparation method thereof; each 100mL medicine contains 0.5-2.0g of antimicrobial peptide, 0.2-1.0g of poloxamer 407 and poloxamer 408, wherein the mass ratio of poloxamer 407 and poloxamer 408 is (1:1) to (1:4), 0.3-1.2g of triethanolamine, 1.5-3.5g of glycerol, 1.0-3.0g of tween-80, 0.01-0.03g of butylated hydroxytoluene, 0.01-0.03g of ethylparaben and distilled water. The medicine prepared by the invention is fast and long-lasting in efficiency, is excellent in slow-release effect and easy to control in dosage.
Description
Technical field
The present invention relates to the medicament of a kind of poultry treatment, particularly a kind ofly treat medicine of fowl bacterial disease and preparation method thereof.
Background technology
Fowl bacterial disease is infected or infectious disease by bacterial one, especially the pyogenic infection caused by gram positive bacteria (as staphylococcus, streptococcus, Diplococcus pneumoniae etc.), pneumonia, pericarditis are extremely serious, larger to livestock and poultry breeding industry harm.For this disease, the most conventional Therapeutic Method is exactly injection of antibiotics.At present, European Union prohibits the use antibiotic, and antibiotic residue problem and generation drug resistance have caused global concern.Antibacterial peptide, as an important component part of animals and plants system of defense, has the advantages such as good stability, green safety, broad-spectrum sterilization, and is obviously better than conventional antibiotic not easily producing in drug resistance.Because current microorganism is to this fact of the extensive drug resistance of conventional antibiotic, the antibiotic finding brand new class is the effective way solving resistance problems, and the evolution course that endogenous antibiotic peptide have passed through millions of years still remains powerful antibacterial efficacy, therefore it may be the optimum selection solving microorganism resistance problems.Antibacterial peptide is because antibacterial activity is high, and kind is many, and alternative scope is wide, and target bacterial strain not easily produces the reasons such as resistant mutation, and is considered to have broad application prospects in pharmaceuticals industry
In recent years, along with going deep into of biopharmaceutical development and pharmacokinetic study, find that solution exists holdup time short, the problem such as bioavailability is low, need to increase administration number of times to improve bioavailability.And improve bioavailability simply by increase administration number of times, easily bring out untoward reaction and have the risk causing toxic reaction.
Gel is a kind of novel pharmaceutical formulation of rising in recent years, is be carrier with hydrophilic polymer, has good biocompatibility, for semi-solid state, can action time of prolong drug, reduce administration number of times, be widely used in the Novel Drug Delivery Systems such as slow release, controlled release and pulse release.Traditional hydrophilic gel, by smearing treatment, does not have practical feasibility to poultry, and dosage is wayward.Injection have dosage accurately, fast, the drug effect of reliable effect, absorption acts on rapidly, but antibacterial peptide class is eliminated soon in vivo, and action time is short.
Summary of the invention
The object of this invention is to provide and a kind ofly treat medicine of fowl bacterial disease and preparation method thereof, have that the holdup time is short, bioavailability is low and the uppity problem of dosage to solve existing medicament.
Technical scheme is as follows:
Treat a medicine for fowl bacterial disease, it is characterized in that, described in every 100mL, the composition of medicine comprises:
Antibacterial peptide 0.5 ~ 2.0g, mass ratio is poloxamer188 and PLURONICS F87 totally 0.2 ~ 1.0g, the triethanolamine 0.3-1.2g of 1:1 ~ 1:4, glycerol 1.5 ~ 3.5g, tween 80 is 1.0-3.0g, di-tert-butyl hydroxy toluene 0.01-0.03g, ethyl hydroxybenzoate 0.01 ~ 0.03g and distilled water.
Further, the solution of described poloxamer188 to be Solute mass fraction be 15%-25%; The solution of PLURONICS F87 to be Solute mass fraction be 5%-15%.
Further, described antibacterial peptide comprises: Gramicidin, poly-D-lysine, lactobacillin, cecropin, alexin, nisin or bacitracin.
Further, described in every 100mL, the composition of medicine comprises:
Described bacitracin 1.0g, mass fraction be 25% poloxamer188 and mass fraction be 10% PLURONICS F87 altogether 0.6g, the mass ratio of described poloxamer188 and described PLURONICS F87 is 1:3, triethanolamine 0.7g, glycerol 2.6g, tween 80 is 2.0g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.03g and distilled water.
Further, described in every 100mL, the composition of medicine comprises:
Described poly-D-lysine 1.8g, mass fraction be 21% poloxamer188 and mass fraction be 6% PLURONICS F87 altogether 0.5g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:1, triethanolamine 0.6g, glycerol 2.3g, tween 80 is 1.6g, di-tert-butyl hydroxy toluene 0.022g, ethyl hydroxybenzoate 0.018g and distilled water.
Further, described in every 100mL, the composition of medicine comprises:
Described lactobacillin 0.9g, mass fraction be 23% poloxamer188 and mass fraction be 9% PLURONICS F87 altogether 0.7g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:3, triethanolamine 0.9g, glycerol 2.7g, tween 80 is 1.9g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.01g and distilled water.
Further, described in every 100mL, the composition of medicine comprises:
Described alexin 2.0g, mass fraction be 22% poloxamer188 and mass fraction be 11% PLURONICS F87 altogether 1.0g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:1, triethanolamine 1.2g, glycerol 1.9g, tween 80 is 1.2g, di-tert-butyl hydroxy toluene 0.016g, ethyl hydroxybenzoate 0.025g and distilled water.
A kind of preparation method for the treatment of the medicine of fowl bacterial disease, it is characterized in that: ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min makes it evenly swelling, obtains the swelling thing of poloxamer; Another that antibacterial peptide is soluble in water, add glycerol, tween 80 stirs, obtain antibacterial peptide solution, antibacterial peptide solution is joined in the swelling thing of poloxamer, then add triethanolamine, stir evenly, be settled to 100ml with distilled water, finally filter and get final product.
Further, described filtration uses microporous filter membrane, aperture≤0.45 μm of described microporous filter membrane.
Further, described medicine preparation is become ejection preparation.
Beneficial effect of the present invention:
1, the medicine prepared of the present invention is according to the different temperatures generation inversion of phases of inside and outside, and external exist in liquid form, transfers gel at once after injection, drug effect rapidly, lasting, overcome the problem that ordinary gel lacks good spreadability;
2, the sustained drug release effect prepared of the present invention is good, is expelled to the holdup time in body to reach 7;
3, the medicine prepared of the present invention is with the mode administration of ejection preparation, overcomes the uppity problem of ordinary gel dosage.
Detailed description of the invention
The present invention is described in detail below in conjunction with embodiment.
In the embodiment of the present invention, medicine holdup time experimental technique in vivo: take barium sulfate as contrast agent, injects medicine of the present invention in rabbit one oviductus lateralis, and opposite side injects physiological saline solution in contrast.Adopt digital radiography systems axiol-ogy Post operation 0,1,2,3,5,7 medicines delay situation in vivo.
In embodiment, medicine degradation experiment method in vitro: by the medical sampling tube of infusion of medicine of the present invention for 0.5ml, 38 DEG C of water bath water-bath 1h, after gelation, taking-up is inserted in 15ml PBS liquid, and PBS liquid is the phosphate buffer containing 0.05% tween 20, and its pH is 7.4; Take out in 1,5 and 7d, clean with distilled water flushing, 80 DEG C of oven dry are weighed to constant weight, are calculated as follows the weight-loss ratio of gel:
Weight-loss ratio=(W1-W2)/W1*100%
Wherein, W1 is the quality before degraded, mg;
W2 is the quality after degraded, mg.
In the present invention, antibacterial peptide includes but not limited to: nisin, bacitracin, Gramicidin, poly-D-lysine, lactobacillin, cecropin, alexin etc.The preferred nisin of the present embodiment and bacitracin.
Embodiment 1
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: nisin 0.5g, mass fraction be 15% poloxamer188 and mass fraction be 5% PLURONICS F87 altogether 0.3g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:2, triethanolamine 0.3g, glycerol 1.5g, tween 80 is 1.0g, di-tert-butyl hydroxy toluene 0.01g, ethyl hydroxybenzoate 0.01g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that nisin is soluble in water, add glycerol, tween 80 stirs, obtain nisin solution, nisin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 64.1%, 5th day weight-loss ratio be the 73.8%, 7th day weight-loss ratio is 95.8%.
Embodiment 2
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: nisin 1.0g, mass ratio is poloxamer188 and the PLURONICS F87 0.6g altogether that the mass fraction of 1:1 is 15%, triethanolamine 0.7g, glycerol 2.6g, tween 80 is 2.0g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.03g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that nisin is soluble in water, add glycerol, tween 80 stirs, obtain nisin solution, nisin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 58.5%, 5th day weight-loss ratio be the 65.3%, 7th day weight-loss ratio is 92.4%.
Embodiment 3
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: nisin 2.0g, mass fraction be 20% poloxamer188 and mass fraction be 10% PLURONICS F87 altogether 1.0g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:4, triethanolamine 1.2g, glycerol 3.5g, tween 80 is 3.0g, di-tert-butyl hydroxy toluene 0.03g, ethyl hydroxybenzoate 0.02g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that nisin is soluble in water, add glycerol, tween 80 stirs, obtain nisin solution, nisin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 57.1%, 5th day weight-loss ratio be the 68.7%, 7th day weight-loss ratio is 93.2%.
Embodiment 4
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: nisin 1.0g, mass fraction be 25% poloxamer188 and mass fraction be 10% PLURONICS F87 altogether 0.6g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:3, triethanolamine 0.7g, glycerol 2.6g, tween 80 is 2.0g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.03g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that nisin is soluble in water, add glycerol, tween 80 stirs, obtain nisin solution, nisin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 56.3%, 5th day weight-loss ratio be the 67.1%, 7th day weight-loss ratio is 91.4%.
Embodiment 5
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: bacitracin 1.0g, mass fraction be 25% poloxamer188 and mass fraction be 10% PLURONICS F87 altogether 0.6g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:3, triethanolamine 0.7g, glycerol 2.6g, tween 80 is 2.0g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.03g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that bacitracin is soluble in water, add glycerol, tween 80 stirs, obtain bacitracin solution, bacitracin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 51.9%, 5th day weight-loss ratio be the 55.7%, 7th day weight-loss ratio is 90.6%.
Embodiment 6
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: Gramicidin 1.3g, mass fraction be 19% poloxamer188 and mass fraction be 8% PLURONICS F87 altogether 0.7g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:2, triethanolamine 0.5g, glycerol 1.9g, tween 80 is 2.1g, di-tert-butyl hydroxy toluene 0.018g, ethyl hydroxybenzoate 0.023g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that Gramicidin is soluble in water, add glycerol, tween 80 stirs, obtain Gramicidin solution, Gramicidin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 52.4%, 5th day weight-loss ratio be the 56.1%, 7th day weight-loss ratio is 90.9%.
Embodiment 7
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: poly-D-lysine 1.8g, mass fraction be 21% poloxamer188 and mass fraction be 6% PLURONICS F87 altogether 0.5g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:1, triethanolamine 0.6g, glycerol 2.3g, tween 80 is 1.6g, di-tert-butyl hydroxy toluene 0.022g, ethyl hydroxybenzoate 0.018g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that poly-D-lysine is soluble in water, add glycerol, tween 80 stirs, obtain Poly-L-Lysine Solution, Poly-L-Lysine Solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 8th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 50.3%, 5th day weight-loss ratio be the 52.8%, 7th day weight-loss ratio is 88.1%.
Embodiment 8
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: lactobacillin 0.9g, mass fraction be 23% poloxamer188 and mass fraction be 9% PLURONICS F87 altogether 0.7g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:3, triethanolamine 0.9g, glycerol 2.7g, tween 80 is 1.9g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.01g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that lactobacillin is soluble in water, add glycerol, tween 80 stirs, obtain lactobacillus cellulose solution, lactobacillus cellulose solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 8th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 50.7%, 5th day weight-loss ratio be the 53.1%, 7th day weight-loss ratio is 88.3%.
Embodiment 9
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: cecropin 1.1g, mass fraction be 23% poloxamer188 and mass fraction be 12% PLURONICS F87 altogether 1.0g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:4, triethanolamine 0.5g, glycerol 1.6g, tween 80 is 1.3g, di-tert-butyl hydroxy toluene 0.03g, ethyl hydroxybenzoate 0.02g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that cecropin is soluble in water, add glycerol, tween 80 stirs, obtain cecropin solution, cecropin peptide solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 56.9%, 5th day weight-loss ratio be the 66.7%, 7th day weight-loss ratio is 91.5%.
Embodiment 10
A kind of medicine for the treatment of fowl bacterial disease, its composition comprises: alexin 2.0g, mass fraction be 22% poloxamer188 and mass fraction be 11% PLURONICS F87 altogether 1.0g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:1, triethanolamine 1.2g, glycerol 1.9g, tween 80 is 1.2g, di-tert-butyl hydroxy toluene 0.016g, ethyl hydroxybenzoate 0.025g, adding distil water is settled to 100ml.
Ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min make it evenly swelling, obtain the swelling thing of poloxamer; Another that alexin is soluble in water, add glycerol, tween 80 stirs, obtain alexin solution, alexin solution is joined in the swelling thing of poloxamer, add triethanolamine again, stir evenly, be settled to 100ml with distilled water, finally namely obtain drug solution with the filtering with microporous membrane of less than 0.45 μm.
Drug solution preparation is become ejection preparation.
Holdup time experiment in the body of medicine: the normal saline after 1 day in control sides fallopian tube disappears, and the medicine of still visible delay in experimental side fallopian tube, hold-up reduces in time, almost all disappears by the 7th day.
The external degradation experiment of medicine: the 1st day weight-loss ratio is the 51.1%, 5th day weight-loss ratio be the 53.6%, 7th day weight-loss ratio is 89.4%.
Embodiment 11
The performance test of medicine of the present invention: 1 ~ 4 with embodiment 4-10 gained medicine for object of study.
1, medicine of the present invention is to the irritant experiment of rabbit
Get rabbit 35, male and female dual-purpose, check, select the rabbit of non-stimulated symptom, be divided into medicine group 1-7 group at random before test in 24h to every animal, medicine group 1-7 is corresponding embodiment 4-10 gained medicine respectively.In rabbit one oviductus lateralis, inject medicine of the present invention, opposite side injects physiological saline solution in contrast.Postoperative 2 days, 7 take out fallopian tube, the visible two oviductus lateralis color and lusters of naked eyes are ruddy, high resilience, smooth mellow and full, thickness is consistent, tube chamber is unobstructed, with surrounding tissue without adhesion, without hydrops suppuration phenomenon; Tissue slice visible tissue clear in structure, mucosal epithelium are column, cilium exists, has no chronic inflammatory cell infiltration.Show that medicine prepared by the present invention is almost non-stimulated to organizing, good biocompatibility.
2, medicine of the present invention is used for the treatment of chicken pneumonia, with embodiment 5 gained medicine for object of study.
7 Japanese instar chickling 50 that choosing is healthy, artificial challenge's staphylococcus aureus in lung.Next day, in chicken group 36 chickens show stretch that neck is dehisced, dyspnea, cough, loss of appetite or the symptom such as not eat.Have minority chicken non-evident sympton, wherein 6 sudden death, are diagnosed as chicken pneumonia.Occurring that 36 chickens of clinical symptoms are divided into three groups at random, be respectively that drug gel prevents and treats group, drug solution prevents and treats group and ceftriaxone sodium solution prevents and treats group.Often group intravenous drug 100ml respectively, is used in conjunction 6 days.
Experimental result: drug gel control group medication 2 days afterwards above symptom obviously alleviates, and after 3 days, symptom disappears substantially, cure rate 100%(12/12); The medication of bacteriocin solution control group after 3 days symptom obviously alleviate, after 5 days, symptom disappears substantially, cure rate 91.7%(11/12); Ceftriaxone sodium solution control group after 7 days symptom obviously alleviate, cure rate 83.3%(10/12).Medicine of the present invention has good preventive and therapeutic effect to the pneumonia caused by poultry staphylococcus aureus as can be seen here, and drug effect is rapid.
3, medicine of the present invention is used for the treatment of pig pyogenic infection, with embodiment 5 gained medicine for object of study.
At injured pig wound injection staphylococcus aureus liquid.Next day, pig local starts the symptom occurring pyogenic infection, spreads all over whole body after several days.To this pig in intramuscular injection medicine of the present invention, be used in conjunction three days, symptom obviously alleviates.After seven days, symptom disappears substantially.As can be seen here, medicine of the present invention has good therapeutic effect to the pyogenic infection caused by poultry staphylococcus aureus.
4, the phase transition temperature test of medicine of the present invention, with embodiment 4-10 gained medicine for object of study.
Adopt test tube roll back method to determine the phase transition temperature of medicine of the present invention, phase transition temperature is 38 DEG C, and viscosity is 1.9pas, and this medicine is in temperature lower than being Newtonian fluid when 38 DEG C, and viscosity is very little; Along with temperature raises, viscosity increases gradually, when temperature is close to 38 DEG C, shows typical pseudoplastic fluid body characteristics; Gel is become when 38 DEG C.
Be solution state under medicine room temperature of the present invention, immediately at agents area generation phase in version after administration, form non-chemically crosslinked semi-solid preparation.Its mechanism of action is that after temperature change, hydrogen bond or hydrophobic interaction change thereupon, causes the physical state of medicine also to change.
5, the steady-state viscosity test of medicine of the present invention
Adopt rotational rheometer to determine the impact of different prescription on medicine steady-state viscosity of the present invention, result shows: along with increasing of poloxamer188 concentration in prescription, and the phase transition temperature of medicine reduces, and viscosity increases; Along with increasing of PLURONICS F87 concentration in prescription, the phase transition temperature of medicine increases, and viscosity reduces.
Above-mentioned 1 ~ 5 experimental result shows, through safety of medicine prepared by present invention process, to no skin irritation, decreases administration number of times, improves compliance, and extends the medicine holdup time in vivo, improves the bioavailability of medicine.
Claims (8)
1. treat a medicine for fowl bacterial disease, it is characterized in that, described in every 100mL, the composition of medicine comprises:
Antibacterial peptide 0.5 ~ 2.0g, mass ratio is poloxamer188 and PLURONICS F87 totally 0.2 ~ 1.0g, the triethanolamine 0.3-1.2g of 1:1 ~ 1:4, glycerol 1.5 ~ 3.5g, tween 80 is 1.0-3.0g, di-tert-butyl hydroxy toluene 0.01-0.03g, ethyl hydroxybenzoate 0.01 ~ 0.03g and distilled water; The solution of described poloxamer188 to be Solute mass fraction be 15%-25%; The solution of PLURONICS F87 to be Solute mass fraction be 5%-15%.
2. the medicine for the treatment of fowl bacterial disease as claimed in claim 1, is characterized in that: described antibacterial peptide comprises: Gramicidin, lactobacillin, cecropin, alexin, nisin or bacitracin.
3. the medicine for the treatment of fowl bacterial disease as claimed in claim 2, is characterized in that: described in every 100mL, the composition of medicine comprises:
Described bacitracin 1.0g, mass fraction be 25% poloxamer188 and mass fraction be 10% PLURONICS F87 altogether 0.6g, the mass ratio of described poloxamer188 and described PLURONICS F87 is 1:3, triethanolamine 0.7g, glycerol 2.6g, tween 80 is 2.0g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.03g and distilled water.
4. the medicine for the treatment of fowl bacterial disease as claimed in claim 2, is characterized in that: described in every 100mL, the composition of medicine comprises:
Described lactobacillin 0.9g, mass fraction be 23% poloxamer188 and mass fraction be 9% PLURONICS F87 altogether 0.7g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:3, triethanolamine 0.9g, glycerol 2.7g, tween 80 is 1.9g, di-tert-butyl hydroxy toluene 0.02g, ethyl hydroxybenzoate 0.01g and distilled water.
5. the medicine for the treatment of fowl bacterial disease as claimed in claim 2, is characterized in that: described in every 100mL, the composition of medicine comprises:
Described alexin 2.0g, mass fraction be 22% poloxamer188 and mass fraction be 11% PLURONICS F87 altogether 1.0g, the mass ratio of poloxamer188 and PLURONICS F87 is 1:1, triethanolamine 1.2g, glycerol 1.9g, tween 80 is 1.2g, di-tert-butyl hydroxy toluene 0.016g, ethyl hydroxybenzoate 0.025g and distilled water.
6. treat the preparation method of the medicine of fowl bacterial disease as claimed in claim 1 for one kind, it is characterized in that: ethyl hydroxybenzoate and di-tert-butyl hydroxy toluene are dissolved in distilled water, under stirring, add poloxamer188 and PLURONICS F87, at 20-30 DEG C, stir 15 ~ 30min makes it evenly swelling, obtains the swelling thing of poloxamer; Another that antibacterial peptide is soluble in water, add glycerol, tween 80 stirs, obtain antibacterial peptide solution, antibacterial peptide solution is joined in the swelling thing of poloxamer, then add triethanolamine, stir evenly, be settled to 100ml with distilled water, finally filter and get final product.
7. the preparation method of the medicine for the treatment of fowl bacterial disease as claimed in claim 6, is characterized in that: described filtration uses microporous filter membrane, aperture≤0.45 μm of described microporous filter membrane.
8. the preparation method of the medicine for the treatment of fowl bacterial disease as claimed in claim 6, is characterized in that: described medicine preparation is become ejection preparation.
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| CN106362139B (en) * | 2016-08-30 | 2019-11-26 | 林州中农颖泰生物肽有限公司 | A kind of vibramycin injection and preparation method thereof |
| CN109771368A (en) * | 2019-02-19 | 2019-05-21 | 湖北伽诺美生物科技有限公司 | A kind of bacteriostatic gel and preparation method thereof |
| CN112595685A (en) * | 2020-12-29 | 2021-04-02 | 中农颖泰林州生物科园有限公司 | A product containing cecropin and method for detecting cecropin content in the product |
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2013
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Non-Patent Citations (3)
| Title |
|---|
| Production of nisin-loaded solid lipid nanoparticles for sustained antimicrobial activity;Prombutara p et al;《food control》;20120430;第24卷(第1-2期);184-190 * |
| 何文等,.壳聚糖对泊洛沙姆液体栓剂基质影响的体外研究.《广东药学院学报》.2005,第21卷(第1期),26-29. * |
| 邹锋.家蝇抗菌肽生产与制剂研究.《中国优秀硕士学位论文全文数据库,农业科技辑,湖南农业大学硕士学位论文》.2008,摘要,第2-3、28、33、39、45-47页. * |
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Denomination of invention: Medicine for treating animal bacterial diseases and preparation method thereof Effective date of registration: 20170726 Granted publication date: 20150128 Pledgee: China Merchants Bank, Limited by Share Ltd, Weifang branch Pledgor: Shandong Sinder Technology Co., Ltd.|Shandong Sinder Animal Vaccine Co., Ltd. Registration number: 2017980000310 |
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